Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study.
María Eugenia OlmedoMartin ForsterVictor MorenoMaría Pilar López-CriadoIrene BrañaMichael FlynnBernard DogerMaría de MiguelJosé Antonio López-VilariñoRafael NúñezCarmen KahattMartin Cullell-YoungAli ZeaiterEmiliano CalvoPublished in: Investigational new drugs (2021)
Background A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC). An expansion cohort further evaluated this combination. Patients and methods Twenty-eight patients with relapsed SCLC after no more than one line of cytotoxic-containing chemotherapy were treated: 18 (64%) with sensitive disease (chemotherapy-free interval [CTFI] ≥90 days) and ten (36%) with resistant disease (CTFI <90 days; including six with refractory disease [CTFI ≤30 days]). Results Ten patients showed confirmed response (overall response rate [ORR] = 36%); median progression-free survival (PFS) = 3.3 months; median overall survival (OS) = 7.9 months. ORR was 50% in sensitive disease (median PFS = 5.7 months; median OS = 11.5 months) and 10% in resistant disease (median PFS = 1.3 months; median OS = 4.6 months). The main toxicity was transient and reversible myelosuppression. Treatment-related non-hematological events (fatigue, nausea, decreased appetite, vomiting, alopecia) were mostly mild or moderate. Conclusion Doxorubicin 40 mg/m2 and lurbinectedin 2.0 mg/m2 on Day 1 q3wk has shown noteworthy activity in relapsed SCLC and a manageable safety profile. The combination is being evaluated as second-line therapy for SCLC in an ongoing, randomized phase III trial. Clinical trial registration www.ClinicalTrials.gov code: NCT01970540. Date of registration: 22 October, 2013.
Keyphrases
- phase iii
- small cell lung cancer
- clinical trial
- acute myeloid leukemia
- end stage renal disease
- acute lymphoblastic leukemia
- open label
- multiple myeloma
- diffuse large b cell lymphoma
- free survival
- phase ii
- ejection fraction
- newly diagnosed
- double blind
- chronic kidney disease
- oxidative stress
- prognostic factors
- randomized controlled trial
- stem cells
- study protocol
- squamous cell carcinoma
- placebo controlled
- weight loss
- mesenchymal stem cells
- subarachnoid hemorrhage
- chemotherapy induced
- preterm birth